The prevalence of obesity has risen significantly in recent decades in developed countries (Fiegal et al. (1998) Int. J. Obesity 22:39-47; Mokdad et al. (1999) JAMA 282:1519-1522). Because obesity is associated with a significantly elevated risk for type 2 diabetes, coronary heart disease, hypertension, and numerous other major illnesses, and overall mortality from all causes (Must et al. (1999) JAMA 282:1523-1529; Calle et al. (1999) N. Engl. J. Med. 341:1097-1105), weight reduction is critical for the obese patient (Blackburn (1999) Am. J. Clin. Nujtr. 69:347-349, Galuska et al. (1999) JAMA 282:1576). Evidence suggests that pharmacotherapy can enhance weight loss when combined with interventions aimed at changing life style (National Heart, Lung and Blood Institute, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report, NIH Publication No. 98-4083, September 1998). Yet, the available pharmacological therapies to facilitate weight loss fail to provide adequate benefit to many obese patients because of side effects, contraindications or lack of positive response (NIH Publication No. 98-4083, supra). Hence, there is impetus for developing new and alternative treatments for management of body weight, percentage body fat, and obesity.
Type II diabetes is brought on by a combination of genetic and acquired risk factors, including obesity, high-fat diet, lack of exercise, and aging. Worldwide, Type II diabetes has become an epidemic, driven by increases in obesity and a sedentary lifestyle, widespread adoption of western dietary habits, and the general aging of the population in many countries. In 1985, an estimated 30 million people worldwide had diabetes. By 2000, this FIGURE had increased 5-fold, to an estimated 154 million people. The number of people with diabetes is expected to double between now and 2025, to about 300 million.
Type II diabetes is characterized by defects in glucose and lipid metabolism. Typically there are perturbations in many metabolic parameters including increases in fasting plasma glucose levels, free fatty acid levels and triglyceride levels, as well as a decrease in the ratio of HDL/LDL. One of the principal underlying causes of diabetes is thought to be an increase in percentage body fat and insulin resistance in peripheral tissues, principally muscle and fat. What is needed is a method for treating excess weight, unwanted gain and increased body fat. Surprisingly, the present invention meets this and other needs.